Methods for preventing and treating motor-related neurological conditions

ABSTRACT

Methods for preventing or treating motor-related neurological conditions include using ocular light therapy in connection with a conventional therapy for a motor-related neurological condition, such as a drug regimen, to adjust levels of melatonin and/or dopamine in the body of a subject. The ocular light therapy may include elevated levels of blue-green light or green light (e.g., light within a wavelength range of 460 nm to 570 nm, 490 nm to 570 nm, about 520 nm to 570 nm, etc.). The ocular light therapy may also include reduced levels of amber, orange and/or red light. Methods for diagnosing motor-related neurological conditions include use of ocular light therapy to cause a subject to temporarily exhibit one or more symptoms of any motor-related neurological condition to which the subject is predisposed, or which the subject may already be experiencing. A temporary increase in such symptoms may be effected by ocular administration of light including increased amounts of amber, orange and/or red light.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/094,510, filed Dec. 2, 2013, and titled “METHODS FOR PREVENTING ANDTREATING MOTOR RELATED NEUROLOGICAL CONDITIONS” (“the '510Application”), which is a continuation of international patentapplication no. PCT/IB2012/002553, filed on Dec. 2, 2013 and titled“METHODS FOR PREVENTING AND TREATING MOTOR-RELATED NEUROLOGICALCONDITIONS (“the '553 PCT Application”), which is a continuation-in-partof international patent application no. PCT/IB2012/001161, filed on May31, 2012 and titled “METHODS FOR PREVENTING AND TREATING MOTOR-RELATEDNEUROLOGICAL CONDITIONS” (“the '161 PCT Application”). The '510application is also a continuation-in-part of the '161 PCT Application,which claims priority to U.S. Provisional Patent Application No.61/491,860, filed on May 31, 2011 and titled “METHODS FOR PREVENTING ANDTREATING MOTOR-RELATED NEUROLOGICAL CONDITIONS” (“the '860 ProvisionalApplication”).

This application is also a continuation-in-part of U.S. patentapplication Ser. No. 12/666,960, filed on Dec. 28, 2009 (“the '960Application”) pursuant to 35 U.S.C. §371 as a national entry ofInternational patent application no. PCT/AU2008/000955, filed on Jun.30, 2008 and titled “TREATMENT OR PROPHYLAXIS OF A NEUROLOGICAL ORNEUROPSYCHIATRIC DISORDERS VIA OCULAR ADMINISTRATION” (“the '955 PCTApplication”), in which a claim for priority has been made pursuant tothe Paris Convention to Australian Patent Application No. 2007-903747,which was filed on Jun. 29, 2007 (“the '747 Australian Application”).

The entire disclosure of each of the '510 application, the '553 PCTApplication, the '161 PCT Application, the '860 Provisional Application,the '960 Application, the '955 PCT Application, and the '747 AustralianApplication is, by this reference, incorporated herein.

TECHNICAL FIELD

The present invention relates generally to methods for preventing ortreating motor-related neurological conditions and, more specifically,to methods that include stimulating a dopaminergic response by the bodyof a subject, which may include adjusting levels of one or more ofmonoamines, such as melatonin, dopamine and serotonin and/or theiranalogs or derivatives within the body of a subject to reduce oreliminate primary and/or secondary symptoms of a motor-relatedneurological condition, or to prevent or treat a motor-relatedneurological condition. In particular embodiments, the present inventionrelates to the use of light therapy in combination with one or moretraditional therapies for adjusting levels of melatonin and/or melatoninanalogs and/or levels of dopamine and/or dopamine derivatives in amanner that reduces or eliminates symptoms of a motor-relatedneurological condition, halts the progression of a degenerativeneurological disease, or prevents or treats a motor-related neurologicalcondition. In embodiments of the present invention, light therapy may beused in conjunction with drug therapy for addressing motor-relatedneurological conditions.

BACKGROUND OF RELATED ART

Motor-related neurological conditions, which are also referred to as“movement disorders,” and other neuropsychiatric disorders typicallyresult from the degeneration of neurons in the central nervous system.As neurons degenerate, their ability to convey or otherwise utilizeneurotransmitters may diminish, a phenomenon known in the art as“decreased amine function.” In particular, in subjects that suffer fromParkinson's disease and many other motor-related neurologicalconditions, the degeneration of neurons of the so-called “nigro-striataldopamine” (NSD) system results in a decrease in the ability of theseneurons to transmit dopamine, decreasing the ability of neurons of theNSD system to communicate with adjacent neurons. This disruption incommunication results in loss of motor control, which is typicallyprogressive and permanent.

Efforts to counteract the loss of motor control include theadministration of dopamine precursors, dopamine analogs andenzyme-modifying drugs (e.g., L-dopa, etc.), which act like dopaminewithout decreasing the natural production of dopamine. By providing theremaining functional neurons of the NSD system with dopamine analogs,the rate at which these neurons can communicate may increase, which mayartificially restore at least some of the lost motor control experiencedby subjects that suffer from motor-related neurological conditions.

SUMMARY

The present invention includes methods for reducing or eliminatingsymptoms of motor-related neurological conditions, or for preventing ortreating motor-related neurological conditions. Methods that incorporateteachings of the present invention may be useful in conjunction withtraditional therapies (e.g., the administration of drugs, etc.), and mayreduce the extent of traditional therapies (e.g., the dosages of drugs,etc.) that are needed to address motor-related neurological conditions“Motor-related neurological conditions,” as used herein, includes bothprimary motor-related neurological conditions, as well as secondaryconditions, or symptoms, that may accompany or result from a primarymotor-related neurological condition. The terms “address” and“addressing,” when used in connection with “motor-related neurologicalconditions,” refer to reducing or eliminating symptoms of amotor-related neurological condition, as well as prevention andtreatment of the motor-related neurological condition itself.

In various embodiments, a method according to the present invention mayinclude addressing a motor-related neurological condition by stimulatinga dopaminergic response by a subject's body and/or adjusting levels ofone or more monoamines, such as melatonin, dopamine, serotonin, andtheir analogs and/or derivatives, within the subject's body. For thesake of simplicity, the term “melatonin,” as used herein, includesmelatonin and analogs of melatonin, while the term “dopamine” includesdopamine and dopamine analogs, derivatives and other dopaminesubstitutes and the term “serotonin” includes serotonin and derivativesand analogs thereof. In some embodiments, a method according to thepresent invention includes addressing (e.g., adjusting, etc.) levels ofone or more of melatonin, serotonin and dopamine in a subject's body.

Amounts or levels of one or more monoamines (e.g., melatonin, serotoninand/or dopamine, etc.) within the body of a subject may be adjusted in amanner that addresses a motor-related neurological condition. The term“adjustment,” as used herein, includes adjusting levels of monoamines inthe body of a subject. The adjustment of one or both of melatonin anddopamine levels in the body of a subject is also referred to herein as“melatonin-dopamine adjustment.” Melatonin-dopamine adjustment withinthe body of a subject may be achieved by regulating production ofmelatonin. As used herein, “regulating” and similar terms include, butare not limited to, reducing melatonin levels and/or levels of dopamine,as well as moderating levels of melatonin and/or dopamine to adjust asubject's melatonin-dopamine profile.

A dopaminergic response may be stimulated in a variety of ways, such asby administering light to the eyes of a subject, a practice that is alsoreferred to as “ocular light therapy.” In various embodiments, ocularlight therapy may include the administration of light including,consisting essentially of, or consisting of blue-green light and/orgreen light (e.g., light within a wavelength range of 460 nm to 570 nm,490 nm to 570 nm, about 520 nm to 570 nm, about 555 nm, etc.) to thesubject. In some embodiments, above-ambient levels (e.g., irradiance, orenergy; photon density; intensity; etc.) of blue-green and/or greenlight may be provided to the subject's eyes. An example of an effectivetechnique for stimulating a dopaminergic response in a subject includesadministering ocular light therapy that includes above-ambient amountsof wavelengths of 520 nm to 570 nm and that lacks ambient orabove-ambient amounts of other wavelengths of visible light to thesubject.

In some embodiments, levels of amber, orange and/or red wavelengths oflight (e.g., visible light having wavelengths of greater than 570 nm,visible light having wavelengths of greater than 570 nm to about 750 nm,etc.) administered to a subject may be less than the levels ofblue-green and/or green wavelengths in the administered light. In otherembodiments, the levels (e.g., irradiance, or energy; photon density;intensity; etc.) of blue-green and/or green light administered to asubject may exceed the corresponding levels of amber, orange and/or redlight administered to the subject. In some embodiments, the levels ofamber, orange and/or red light administered to a subject may be at mostabout half the levels of blue, blue-green and/or green light that areadministered to the subject. Alternatively, or in addition, levels ofone or more of amber, orange and red wavelengths of light may simulateor fall below the levels of amber, orange and/or red wavelengths oflight that are present in standard indoor lighting, or the “ambient”densities of one or more of amber, orange and/or red wavelengths oflight for any particular narrow band isolated intensity present inambient light to which a subject is normally exposed, etc.).

By administering ocular light therapy in accordance with one or more ofthe teachings above, monitoring a subject's condition and response toocular light therapy, and adjusting one or both of the ocular lighttherapy and drug therapy administered to the subject, the subject'sdopaminergic response may be stimulated, which may vary monoamine (e.g.,melatonin, dopamine and/or serotonin, etc.) levels in the body of thesubject, in a manner that addresses a motor-related neurologicalcondition. In some embodiments, such administration, monitoring andadjustment may include a reduction in traditional therapies (e.g., thedosages of drugs, such as dopamine derivatives and/or drugs foraddressing the side-effects of dopamine derivatives, etc.) that havebeen used to address the motor-related neurological condition. In someembodiments, the amounts of one or more monoamines in the subject's bodyor produced by the subject at one or more particular times during theday may be adjusted. In other embodiments, the amounts of one or moremonoamines present within the subject's body or produced by the subjectthroughout the day, or one or more parts of the subject's monoamineprofile, may be antagonized, moderated or manipulated. In a moreparticular embodiment, one or more parts of the subject's monoamineprofile may be antagonized, moderated or manipulated to resemble a“normal” monoamine profile; e.g., the monoamine profile of a healthysubject, of a subject that does not suffer from a motor-relatedneurological condition, or the subject's monoamine profile during anearlier time of day. Moderation of a subject's monoamine profile mayinclude administration of dopaminergic stimulation therapies ormonoamine regulation therapies (e.g., light therapy, etc.) at one ormore times each day.

In one aspect, the present invention includes, consists essentially ofor even consists of the use of light therapy methods for preventing ortreating at least one motor-related neurological condition. Examples ofsuch conditions include, but are not limited to, Huntington's chorea,periodic limb movement syndrome, restless leg syndrome, nocturnalmyoclonus, Tourette's syndrome, Sundowner's syndrome, REM Sleep BehaviorDisorder, schizophrenia, Pick's disease, Punch drunk syndrome,progressive subnuclear palsy, multiple systems atrophy, corticobasilardegeneration, vascular Parkinsonism, Lewy body dementias, diffuse Lewybody disease, Parkinson's plus syndrome, Korsakow's (Korsakoff's)syndrome, multiple sclerosis, medication-induced motor disorders,drug-induced Parkinson's disease, neuroleptics-induced Parkinson'sdisease, acute dystonia, stroke-post ischemic Parkinsonism,trans-ischemic attack, akathisia dyskinesia and tardive dyskinesia.Disorders characterized by features that typify those expressed assecondary symptoms in Parkinson's disease patients and other diseases inwhich dopamine, serotonin or noradrenaline function is altered may alsobe treated in accordance with teachings of the present invention.Nonlimiting examples of secondary symptoms include Alzheimer's disease,dementia, depressive pseudo dementia, hydrocephalic dementia, dementiaassociated with Parkinson's disease, anxiety, generalized anxietydisorder, panic disorder, agoraphobia, obsessive-compulsive disorder,post-traumatic stress disorder, acute stress disorder, depression,bipolar disorder, various personality and insomnia disorders.

In another aspect, the present invention includes the use of lighttherapy in conjunction with traditional therapies for motor-relatedneurological conditions. Thus, light therapy may be used in conjunctionwith drug treatment, cellular (e.g., fetal cell, stem cell, etc.)therapies, surgical treatments and/or other therapies for addressingmotor-related neurological conditions. Ocular light therapy may beadministered in conjunction with melatonin agonists or antagonists toadjust a subject's melatonin levels.

The present invention also includes systems in which light therapyapparatuses are used in conjunction with traditional therapies.

Use of light therapy to stimulate a dopaminergic response by a subject'sbody, which may affect monoamine (e.g., melatonin-dopamine, etc.)adjustment in the body of a subject, in conjunction with monitoring ofthe subject's response to the light therapy, may also enable a physicianto reduce a dosage of one or more drugs prescribed for and administeredto a subject suffering from a motor-related neurological condition,while, in some instances, having a disease-modifying effect (e.g.,slowing or halting progression of the condition, etc.). The course oftreatment for a particular subject that suffers from a motor-relatedneurological condition may be revised to decrease the need forconventional treatment of the motor-related neurological condition(e.g., to decrease the dosage of one more drugs (e.g., a dopamineanalog, an analog of another neurotransmitter, etc.), etc., administeredto that subject). In some embodiments, when light therapy is used inconjunction with drugs to treat a motor-related neurological condition,a physician may prescribe a lower-than-normal dosage of the drugs (i.e.,a lower-than-normal dosage of a drug that is typically required whenmonoamine production (e.g., melatonin production, etc.) is notregulated). When light therapy is coupled with drug therapy, a physicianmay define a succinct and strategic controlled therapy package that, insome cases, may be tailored to a particular subject.

In another aspect, the present invention includes standardization amongvarious dopamine replacement therapies and as to how much of any variousdopamine replacement therapies any given patient should receive. Forexample, a daily dosage of 1000 mg of one medication may be theequivalent of a 650 mg daily dosage of another medication. Because theuse of light therapy in accordance with teachings of the presentinvention enables a reduction in dosages of dopamine replacementmedication, a drug conversion table may be used to standardizeequivalent doses for various dopamine replacement medications. In thisway, an effective reduction in the required dosage of a dopaminereplacement medication can be achieved regardless of the medicine used.Such a table, titled a “Total Drug Burden” or “TDB” table, is providedin FIG. 22.

The present invention also includes techniques for diagnosingmotor-related neurological conditions. In such a technique, increasedlevels of one or more of amber, orange and red light may be administeredto a subject. In some embodiments, the colors and intensities of lightadministered to the subject may be about the same as or greater thanlevels of the same color or colors of light present at dusk. The lightmay be administered ocularly. Administering one or more of amber, orangeand red light to the subject may cause the subject to temporarilyexhibit symptoms of one or more motor-related neurological conditionsbefore such symptoms would otherwise present themselves. The discoveryof such conditions following the administration of amber, orange and/orred light in accordance with teachings of the present invention mayenable a physician to make a pre-diagnosis or an early diagnosis of amotor-related neurological condition. In the event that a physiciandetermines that the subject is likely to suffer or will suffer from amotor-related neurological condition, the physician may prescribe acourse of treatment for the diagnosed condition. A prescribed course oftreatment may include, among other things, use of suitable ocular lighttherapy, etc., the administration of one or more drugs, and/or othersuitable treatments.

Other aspects, as well as features and advantages of various aspects, ofthe present invention will become apparent to those of ordinary skill inthe art through consideration of the ensuing description and theappended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

FIGS. 1-4 are charts illustrating the effects of various treatmentregimens that incorporate teachings of the present invention on subjectsthat suffer from motor-related neurological conditions;

FIG. 5 illustrates the actions of a subject during a fist to elbowlatency test;

FIG. 6 illustrates the actions of a subject during a knee to floorlatency test;

The charts of FIGS. 7-15 depict the effects of long-term light therapyon the symptoms of subjects who suffer from motor-related neurologicalconditions—specifically demonstrating that when light therapy and drugtherapy are combined, the progression of degenerative neurologicaldiseases may be slowed or halted;

FIGS. 16 and 17 are charts showing the unfiltered spectral powerdistribution for a polychromatic light source and the filtered spectralpower distribution for the same polychromatic light source,respectively;

FIGS. 18 and 19 are charts illustrating the effects of long-term lighttherapy—specifically, light predominantly including a narrow bandisolated intensity of green light—on subjects who suffer frommotor-related neurological conditions;

FIG. 20 is a chart that compares the average drug dosages required bysubjects who suffer from motor-related neurological disorders at theoutset of a prolonged light therapy study to the average drug dosagesrequired by the subjects at the end of the prolonged light therapystudy;

FIGS. 21 and 22 are charts demonstrating the utility of red light inenabling the early diagnosis of motor-related neurological conditions;and

FIG. 23 is a chart depicting equivalent dosages for a variety ofdopamine derivatives.

DETAILED DESCRIPTION

Ambient light provides a reference point for the manner in which lightmay be administered to a subject in accordance with teachings of thepresent invention. The phrase “ambient light” refers to an amount orlevel of light, such as an intensity, a photon density, or anirradiance, or energy, of light. “Ambient light” may refer to acollection of wavelengths of visible light, such as those present inso-called “white light,” which is more accurately referred to as“polychromatic light,” or in narrower bandwidths (e.g., colors, etc.) oflight. As will become more apparent from the ensuing description, it maybe beneficial in some embodiments of the present invention to expose asubject to above-ambient levels of some wavelengths of light, whilelimiting the subject's exposure to other wavelengths of light tobelow-ambient levels.

As used herein, the phrase “ambient level” may refer to an average ofthe level or amount of a particular bandwidth of light in ambient indoorlighting. Standard indoor lighting is generally white light, orpolychromatic light, having an intensity of about 50 lux to about 500lux. Ambient indoor lighting may comprise standard indoor fluorescentlighting or standard indoor incandescent lighting.

The “average” level or amount of light of a particular bandwidth mayinclude an average of the level or amount of that bandwidth in ambientindoor lighting at about 50 lux and the level or amount of thatbandwidth in ambient indoor lighting at about 500 lux. Levels of variousbandwidths of light may be considered to be “above-ambient” when theyexceed the ambient levels of the same wavelengths of light present inambient indoor lighting. Conversely, levels of various wavelengths oflight are considered to be “below-ambient” when they are less than theambient levels of the same wavelengths of light present in the same typeof ambient indoor lighting.

As a point of reference, standard incandescent indoor lighting, whichhas a collective ambient intensity of about 50 lux to about 500 lux, iscomposed primarily of amber and red wavelengths of light, with somegreen light, which makes up only a small portion of the spectrum outputby standard incandescent indoor lighting. Standard fluorescent indoorlighting has the signature of mercury, with three peaks: a first peak inthe indigo-deep blue range (435 nm-436 nm); a second peak in thegreen-yellow range (540 nm-560 nm); and a third peak at the redwavelength of 640 nm. The deep blue and green-yellow peaks of such lightare, of course, less intense, photon-dense or luminescent, or energetic,than the collective intensity of light output by standard fluorescentindoor lighting.

At about 50 lux, standard indoor lighting (incandescent and/orfluorescent) has a collective photon density of 3.70×10¹³ photons/cm²/sand a collective irradiance of 13.2 μW/cm² (or 1.32×10⁻⁵ W/cm²). Theblue-to-green (e.g., 460 nm to 570 nm, etc.) portion of the spectrum ofabout 50 lux standard indoor lighting has a photon density of 1.35×10¹³photons/cm²/s and an irradiance of 5.1 μW/cm². These values, as well asthe photon density and irradiance of narrower wavelength ranges in theblue-to-green in standard indoor lighting having an intensity of about50 lux, are included in the following table:

TABLE 1 Standard Indoor Light at About 50 lux Photon Density IrradianceColor/Wavelength Range (photons/cm²/second) (μWatts/cm²) LuxPolychromatic (white) 3.70 × 10¹³ 13.2 47 Blue (460 nm to 500 nm) 3.31 ×10¹² 1.4 2 Green (500 nm to 570 nm) 1.03 × 10¹³ 3.8 22 Blue-to-Green1.35 × 10¹³ 5.1 23 (460 nm to 570 nm) 490 nm to 565 nm 1.02 × 10¹³ 3.820 520 nm to 565 nm 7.25 × 10¹² 2.6 17 525 nm to 555 nm 4.81 × 10¹² 1.811 520 nm to 539 nm 2.68 × 10¹² 1.0 6

The amber-to-red (e.g., above 570 nm to 750 nm, etc.) portion of thespectrum of about 50 lux standard indoor lighting has an intensity ofabout 24 lux, a photon density of 2.04×10¹³ photons/cm²/s and anirradiance of 6.7 μW/cm². The irradiance of amber-to-red light instandard indoor lighting at about 50 lux exceeds the irradiance of theblue-to-green “effective” spectrum of standard indoor lighting at about50 lux.

At about 500 lux, the collective photon density of standard indoorlighting is 3.69×10¹⁴ photons/cm²/s and the collective irradiance ofstandard indoor lighting is 133.5 μW/cm². At about 500 lux, theblue-to-green portion of the standard indoor lighting spectrum has aphoton density of 1.53×10¹⁴ photons/cm²/s and an irradiance of 58.4μW/cm². These values, as well as the photon density and irradiance ofnarrower wavelength ranges in the blue-to-green in standard indoorlighting having an intensity of about 500 lux, are included in thefollowing table:

TABLE 2 Standard Indoor Light at About 500 lux Photon Density IrradianceColor/Wavelength Range (photons/cm²/second) (μWatts/cm²) LuxPolychromatic (white) 3.69 × 10¹⁴ 133.5 479 Blue (460 nm to 500 nm) 4.09× 10¹³ 16.9 18 Green (500 nm to 570 nm) 1.14 × 10¹⁴ 42.0 238Blue-to-Green 1.53 × 10¹⁴ 58.4 256 (460 nm to 570 nm) 490 nm to 565 nm1.15 × 10¹⁴ 42.9 223 520 nm to 565 nm 7.79 × 10¹³ 28.5 181 525 nm to 555nm 5.14 × 10¹³ 18.9 121 520 nm to 539 nm 3.03 × 10¹³ 11.4 66

The amber-to-red portion of the spectrum of about 500 lux standardindoor lighting has an intensity of about 225 lux, a photon density of1.85×10¹⁴ photons/cm²/s and an irradiance of 60.4 μW/cm². The irradianceof amber-to-red light in standard indoor lighting at about 500 luxexceeds the irradiance of the blue-to-green “effective” spectrum ofstandard indoor lighting at about 500 lux.

Based on the foregoing, when “ambient” includes an average of the levelof one or more bandwidths of light in polychromatic light of about 50lux and the level of the same bandwidth(s) of light in polychromaticlight of about 500 lux, the ambient levels of the bandwidths set forthin TABLES 1 and 2 may include the ambient values for standard indoorlighting identified in TABLE 3.

TABLE 3 Average Ambient Levels of Standard Indoor Light Photon DensityIrradiance Color/Wavelength Range (photons/cm²/second) (μWatts/cm²) LuxPolychromatic (white) 2.03 × 10¹⁴ 73.4 263 Blue (460 nm to 500 nm) 2.21× 10¹³ 9.1 10 Green (500 nm to 570 nm) 6.19 × 10¹³ 22.9 130Blue-to-Green 8.35 × 10¹³ 31.8 140 (460 nm to 570 nm) 490 nm to 565 nm6.24 × 10¹³ 23.4 122 520 nm to 565 nm 4.26 × 10¹³ 15.6 99 525 nm to 555nm 2.81 × 10¹³ 10.3 66 520 nm to 539 nm 1.65 × 10¹³ 6.2 36

The amber-to-red portion of the spectrum of ambient standard indoorlighting has an intensity of about 125 lux, a photon density of1.03×10¹⁴ photons/cm²/s and an irradiance of 33.6 μW/cm². The irradianceof amber-to-red light in standard indoor lighting of average intensityexceeds the irradiance of the blue-to-green “effective” spectrum ofstandard indoor lighting at average intensity.

As an alternative to defining “ambient” in terms of an average,“ambient” light may include polychromatic light within a range ofintensities, photon densities and/or irradiances, or energies, alongwith the levels of light within various bandwidths of polychromaticlight within such a range. Levels of various wavelengths of light may beconsidered to be “above-ambient” when they exceed the same levels of thesame wavelengths of light in an ambient range. Conversely, levels ofvarious wavelengths of light may be considered to be “below-ambient”when they are less than the same levels of the same wavelengths of lightpresent in the ambient range. For purposes of this disclosure, the lowend of “ambient” levels may comprise the levels of each wavelength rangepresent in about 50 lux polychromatic light, while the high end of“ambient” levels comprises the levels of various wavelength rangespresent in about 500 lux polychromatic light. With this definition ofambient, below-ambient levels would include below-about 50 lux levels,while above-ambient levels would include above-about 500 lux levels.

A method for addressing motor-related neurological conditions inaccordance with teachings of this present invention includesadministering light therapy to a subject who suffers from, is believedto be suffering from, or is at risk for a motor-related neurologicalcondition. Light therapy may be administered in a manner that stimulatesa dopaminergic response by the subject, which may adjust levels of oneor more monoamines (e.g., melatonin, serotonin, dopamine, etc.) in thebody of the subject. The administration of light therapy may beconducted in conjunction with the administration of conventionaltherapies, including, but not limited to, the administration of dopaminederivatives or other drugs for addressing motor-related neurologicalconditions. In addition to administering light therapy, a method of thepresent invention may include evaluating the effect of the light therapyon the subject's symptoms, if any. In cases where light therapyaddresses the subject's symptoms, any conventional therapies used inconjunction with the light therapy may be adjusted (e.g., decreased,etc.) in response to the effects of light therapy on the subject. Theuse of light therapy that incorporates teachings of the presentinvention, with or without conventional therapy for addressingmotor-related neurological conditions, may stimulate a dopaminergicresponse by the subject's body, which, among other things, may adjustlevels of one or more monoamines within the subject's body (e.g., levelsof melatonin in the body of a subject relative to dopamine levels in thesubject's body, including levels of melatonin and dopamine within thebrain of the subject, etc.).

Ocular light therapy may include the administration of light includingblue-green and/or green wavelengths of light to the subject. In someembodiments, the light that is administered to the subject includesabove-ambient levels of blue-green and/or green wavelengths. Lighttherapy that employs ambient or below-ambient levels of blue-greenand/or green wavelengths is also within the scope of the presentinvention.

The blue-green and/or green light that is administered to the subjectmay be administered as blue-green light and/or green light or othertypes of light (e.g., polychromatic light, etc.) that includeabove-ambient levels of green light or blue-green light, or light thatis predominantly blue-green and/or green. Nonlimiting examples includecolors of light with above-ambient levels of wavelengths that are withina wavelength range of 460 nm to 570 nm, 490 nm to 570 nm, about 520 nmto 570 nm, about 525 nm to about 555 nm, above 520 nm to less than 540nm, or any wavelength within any of these ranges.

In some embodiments, a narrow portion of the spectrum of visible lightmay be administered to the subject. Without limiting the scope of thepresent invention, the light administered to the subject may consistessentially of (i.e., with the possible addition of colors orwavelengths of visible light directly adjacent to a blue-green and/orgreen band) blue-green and/or green light, or consist of blue-greenand/or green light.

Other embodiments of the method include administering blue-green and/orgreen light to the subject as part of light that comprises a pluralityof different colors, or so-called “polychromatic light.” In morespecific embodiments, the polychromatic light may comprise so-called“white light.” In some embodiments, including those where polychromaticlight that includes a peak in the blue, blue-green and/or greenwavelengths is delivered to a subject's eyes, the light may be deliveredat an above-ambient intensity (including an intensity of about 500 luxor more, an intensity of about 1,000 lux or more, an intensity of about1,500 lux or more, an intensity of about 4,000 lux or more, an intensityof about 5,000 lux or more, etc.).

Administration of polychromatic light may include omission of one ormore wavelengths of light or elimination of one or more wavelengths frompolychromatic light before the light reaches the subject's eyes, or isadministered to the subject. In some embodiments, the elimination of oneor more wavelengths of light from polychromatic light, including whitelight, may be accomplished by filtering. Filtering may reduce one ormore colors or wavelengths of light to below-ambient levels (e.g., to anintensity of about 50% or less of a combined intensity of therapeuticlight, such as light having wavelengths of 460 nm to 570 nm, etc.).Alternatively, filtering may substantially remove, or even completelyremove, one or more colors or wavelengths of light from thepolychromatic light. Filtration of one or more wavelengths frompolychromatic light may be based on any of a number of factors. Oneembodiment of a factor upon which filtering may be based is theundesirability of one or more wavelengths (e.g., amber, orange, red,etc.).

Examples of undesirable wavelengths of light include wavelengths orcolors of light that decrease the therapeutic effects of certainwavelengths of visible light (e.g., by canceling or opposing theactivating effects of the therapeutic wavelengths of visible light,etc.), wavelengths or colors of light that are known to enhance orexacerbate symptoms of one or more motor-related neurologicalconditions, wavelengths or colors of light that may interfere with asubject's ability to exhibit a dopaminergic response or disrupt themonoamine profile in the subject's body (e.g., the subject's brain,etc.) (e.g., the melatonin-dopamine balance in the subject's body,etc.), and even wavelengths or colors of light that provide no apparentbenefit when administered to a subject who suffers from, is believed tosuffer from, or is at risk for suffering from a motor-relatedneurological condition. It has recently been found that light withwavelengths of light that are longer than those of green light (e.g.,light having wavelengths of greater than 570 nm, from greater than 570nm to about 750 nm, amber, orange, and/or red wavelengths of light,etc.) enhance or exacerbate symptoms of motor-related neurologicalconditions.

The bandwidth of light that is reduced omitted or eliminated maycomprise one or more of amber light, orange light and red light, or atleast one wavelength of one or more the foregoing may be omitted orfiltered. In more particular embodiments, visible light havingwavelengths of greater than 570 nm, visible light having wavelengths ofgreater than 570 nm to about 750 nm, etc., may be filtered frompolychromatic light prior to its administration to a subject. In a morespecific embodiment, a filter may be used to reduce the amounts ofvisible light having wavelengths above 570 nm to below-ambient levels.In some embodiments, when ambient or below-ambient levels of blue-greenand/or green light are administered to a subject, the levels ofblue-green and/or green light may exceed the levels of amber, orangeand/or red wavelengths of light administered (e.g., exceed a 1:1 ratio,by a ratio of about 2:1 or more, etc.). A filter that reduceswavelengths above 570 nm to below-ambient levels may allow ambient orabove-ambient amounts of light of one or more wavelengths from 520 nm to570 nm to pass therethrough. In some embodiments, visible light havingwavelengths below 520 nm may also be filtered, and may restrict ocularlight therapy to ambient or above-ambient amounts of one or morewavelengths of 520 nm to 570 nm.

The administration of light therapy to a subject in accordance withteachings of the present invention may be effected at one or more timesduring the day. In some embodiments, the light therapy may beadministered at the same time or times, or substantially the same timeor times, each day. The time or times of day at which light therapy isprovided may be regulated, as may the intensity (e.g., photon density,etc.) of one or more wavelengths of light administered to the subject.

Light therapy may be administered to the subject in accordance with anoptimal dosing schedule. The optimal dosing schedule may, in someembodiments, include light therapy once a day. In some embodiments, theoptimal dosing schedule for light therapy may include administering thelight therapy in the evening (e.g., at a time of day when melatoninlevels are typically increasing, etc.). In a specific, but nonlimiting,embodiment, the optimal dosing schedule may include administration oflight therapy an hour-and-a-half or more after the final administrationof drugs to the subject during the day. In a more specific embodiment,light therapy may be administered between about 5:00 p.m. and about 3:00a.m. or, even more specifically, between about 7:00 p.m. and about 10:00p.m. The intensity (e.g., a photon density of about 10¹³ photons/cm²/sto about 10¹⁶ photons/cm²/s, etc.) and the duration (e.g., about onehour, about thirty minutes, etc.) of the light therapy may be tailoredto reduce melatonin levels without adversely affecting the subject'ssleep patterns, or circadian rhythms.

In other embodiments, light therapy may be administered at a pluralityof different times throughout each day. The intensity and duration ofeach treatment may be tailored to provide a desired effect at aparticular time during the day, with two or more of the treatmentsdiffering (e.g., in color, intensity, duration, etc.) from one another.Alternatively, all of the light therapy treatments administered duringthe twenty-four (24) hour day may be the same as or substantially thesame as (i.e., with any variance attributable merely to unintendedfluctuations in intensity, time, etc.) the other treatments administeredduring that day.

Light therapy in accordance with teachings of the present invention mayslow or halt the progression of a motor-related neurological disorderafter a few treatments, or positive results may not be seen until lighttherapy is administered for longer periods of time (e.g., weeks, months,etc.). In any event, light therapy may be used as a long-term (e.g., sixmonths, years, the remainder of a subject's life, etc.) treatment.

In some embodiments, light therapy may be used alone to prevent or treata motor-related neurological condition. Stated another way, treatment ofthe motor-related neurological condition may consist of light therapy.

Alternatively, light therapy may be administered in conjunction with theadministration of one or more other treatments for motor-relatedneurological conditions. In some embodiments, these other treatmentscomprise traditional therapies, such as cellular therapies (e.g., withfetal cells, stem cells, etc.), surgical treatments, and the like.

In embodiments where light therapy is administered to a subject inconnection with drug therapy, or pharmacological treatment, the drugsmay include medications intended for treatment of motor-relatedneurological conditions and/or the symptoms of such conditions.Non-limiting examples of such drugs include those that target thedopamine (DA), noradrenaline (NA) and serotonin (5HT) systems, as wellas other drugs identified in FIG. 21. FIG. 21 illustrates the equivalentdaily dosage ranges for a variety of dopamine replacement therapies,including daily dosages of such therapies that are considered to be low(between the first two continuous vertical lines), medium (between thesecond and third continuous vertical lines) and high (between the thirdand fourth continuous vertical lines). The added use of light therapymay enable a physician to prescribe lower than normal dosages (i.e.,drug dosages that are typically required when melatonin production isnot regulated) of these drugs to treat the diagnosed motor-relatedneurological condition. For example, a dosage of a particular dopaminereplacement therapy that would normally (i.e., without light therapy) bein the “high” range may, with light therapy in accordance with teachingsof the present invention, be reduced to the “medium” or “low” range forthe same drug, or to the “medium” or “low” range for another drug listedon the Total Drug Burden table. Similarly, the use of light therapy mayenable a reduction in normally “medium” range dosages to dosages in the“low” range. Reducing the dosages of drug therapies may also reduce oreliminate the side-effects of the drugs, along with the need foradditional drugs to treat any side-effects.

In some embodiments, the times at which drugs are administered in anoptimal dosing schedule are distinct from the time or times of the dayat which light therapy is administered. In a more specific embodiment,drug treatment in accordance with an optimal dosing schedule may occurduring a first part of the day, while light therapy is administeredduring a second part of the day. For example, drugs may be administeredduring the day, while administration of light therapy occurs during theevening. In a more specific embodiment, drug administration may startsometime during the morning (e.g., about thirty minutes before asubject's symptoms would otherwise (without taking the drugs) typicallyappear) and be complete by 5:30 p.m., while light therapy isadministered between 7:00 p.m. and 10:00 p.m.

A number of specific embodiments of dosing and treatment methods are setforth in TABLES 7-13. In those embodiments, light therapy, in the formof polychromatic light having peaks at about 435 nm to about 436 nm,about 460 nm to about 520 nm, about 540 nm to about 560 nm, and about640 nm was administered at an intensity of about 1,000 lux to about1,500 lux. The irradiance of the blue-green light present in the lightadministered to each subject was about 280 μW/cm², while the irradianceof the red light present in that light was only about 150 μW/cm².Although TABLES 7-13 provide many specifics, it should be understoodthat the details, particularly those concerning the use of polychromaticlight (in reference to white light), its intensity, and the duration ofthe light therapy each day, pertain to specific embodiments of thedisclosed protocols.

TABLE 4 sets forth a procedure by which light and drug (dopamine (DA)replacement, or DA agonist) therapies may be tailored for a new (denovo, or “DN”) patient, who has been recently diagnosed with Parkinson'sdisease (PD).

TABLE 4 Example Conditions for Photo-Pharmacological Rule Interventionin A de novo Patient DN1. In de novo patients, the commencing doseshould be 50 Commencing mg of levodopa twice daily at, for example,10:00 a.m. Dose and 4:00 p.m. If the patient's responsiveness tolevodopa diminishes over time, the dose of levodopa can be increased to50 mg three times per day, say at the 8:00 a.m., 1:30 p.m., and 5:30p.m. If the therapeutic effect continues to diminish during the day,each dose may be increased by increments of ¼ to ½ at eachadministration. DN2. First If a patient experiences a symptom-freeperiod upon Dose wakening, the first task is to identify the time whenthe PD symptoms first appear. The first dose of the day should then beadministered approximately 30 minutes prior to the time identified. Asthis may change with continued phototherapy, the time of first doseshould be adjusted accordingly. DN3. Last The last daily dose of DAreplacement should not Dose occur any later than 5:30 p.m. DN4. OptimalThree doses of DA replacement per day: Example Frequency and times of8:00 a.m., 1:30 p.m., and 5:30 p.m. Time of Dosing DN5. Total dailydosage should peak at no more than 600 mg Escalation to per day in threeequally divided lots. If other DA Ceiling dose. replacement drugs aretaken concomitantly, they should not exceed three doses. DN6. Time ofExposure to light should commence between the hours Phototherapy of 7:00p.m. and 10:00 p.m. Drug regimens should not be altered until anobservation period of 2-4 weeks has been undertaken and the patient isin compliance. DN7. Duration The duration of phototherapy should lastfor 1 hour and of should be undertaken daily. Phototherapy DN8. Thefrequency of emission should be polychromatic Frequency and light withan intensity of about 1,000 lux to about Intensity of 1,500 lux.Emission

In TABLE 5, a protocol for incorporating light therapy into an existingdrug (pharmacological) treatment regimen is described.

TABLE 5 Example Conditions for Photo-Pharmacological Intervention in APatient Undergoing Pharmacological Rule Treatment T1. Treatment Inpatients that have been maintained on DA replacement Response therapyfor at least two years, it is first important that the Stabilizationpatient experience some stability in their therapeutic (TRS) response totheir drug regimen prior to commencing added treatment with lighttherapy. This requires professional assessment and stabilization for aperiod of time from 4-8 weeks. T2. First Dose If a patient experiences asymptom-free period upon wakening, the first task is to identify thetime when the PD symptoms first appear. The first dose of the day shouldthen be administered approximately 30 minutes prior to the timeidentified. T3. Last Dose The last daily dose of DA replacement shouldnot occur any later than 5:30 p.m. A patient should not be woken to takemedication. If dosing occurs after 5:30 p.m. then the dose should beincrementally reduced in size until it is eliminated (e.g., by 9:00p.m.). Substitute doses may be inserted during the light therapy phaseof treatment or by increasing other existing doses increased tocompensate for any missed treatment. T4. Optimal Three doses of DAreplacement therapy per day: Example Frequency and times of 8:00 a.m.,1:30 p.m., and 5:30 p.m. Existing Time of times of drug administrationcan be moved by half hour Dosing increments to achieve a balance betweenoptimal therapeutic effects and minimal side effects and to approximatethe optimal dosing regimen. T5. Ceiling Patients on doses larger than600 mg of DA replacement dose therapy per day in three equally dividedlots can incrementally reduce their total dose of DA replacement therapyby ¼ to ½ dose increments while balancing therapeutic effects andadverse effects. T6. Time of Exposure to light should commence betweenthe hours of Phototherapy 7:00 p.m. and 10:00 p.m. Drug regimens shouldnot be altered until an observation period of 2-4 weeks has beenundertaken and the patient is in compliance. T7. Duration of Theduration of phototherapy should last for 1 hour and Phototherapy shouldbe undertaken daily. T8. Frequency The frequency of emission should bepolychromatic light and Intensity of with an intensity of about 1,000lux to about 1,500 lux. Emission

As is apparent from TABLE 5, in addition to therapies that include theadministration of drugs in conjunction with light therapy, the presentinvention includes methods for reducing the dosages of drugsadministered in the treatment of motor-related neurological conditions.Thus, the course of pharmacological treatment for a subject that suffersfrom a motor-related neurological condition may be revised to decreasethe subject's dependence on one more drugs (e.g., a dopamine analog, ananalog of another neurotransmitter, etc.).

A reduction in the dosage of drugs administered to a subject thatsuffers from a motor-related neurological condition is particularlydesirable when the subject suffers from side effects of the drugs. As anexample, PD patients may experience dyskinesia, hyperkinesia or otherside effects of DA replacement therapy. These side effects are typicallydue to overdosing. An example of a procedure for reassessing andtreating PD and these side effects with drug and light therapies isdescribed by TABLE 6.

TABLE 6 Example Conditions for Photo-Pharmacological Intervention in APatient Experiencing Hyperkinesia or Rule Dyskinesia afterPharmacological Treatment D1. Treatment In patients that have beenmaintained on DA Response replacement therapy for at least two years, itis first Stabilization important that the patient experience somestability in (TRS) their therapeutic response to their drug regimenprior to commencing added treatment with light therapy. This requiresprofessional assessment and stabilization for a period of time from 4-8weeks. D2. First Dose If a patient experiences a symptom-free period atany time during the day or night, the first task is to identify the timewhen the PD symptoms first appear. Doses of DA replacement the dayshould be administered strategically around the time identified. D3.Last Dose The last daily dose of DA replacement should not occur anylater than 5:30 p.m. A patient should not be woken to take medication.If dosing occurs after 9:00 p.m. then the dose should be incrementallyreduced in size until it is eliminated. Substitute doses may be insertedduring the light therapy phase of treatment or by increasing otherexisting doses increased to compensate for any missed treatment. D4.Optimal Three doses of DA replacement therapy per day: Frequency andExample times of 8:00 a.m., 1:30 p.m., and 5:30 p.m. Time of Existingtimes of drug administration can be moved by Dosing half hour incrementsto achieve a balance between optimal therapeutic effects and minimalside effects and to approximate the optimal dosing regimen. Ifadditional doses are required, they should be inserted at timesdetermined after detailed monitoring of therapeutic effects versusadverse side effects. D5. Ceiling Patients on doses larger than 600 mgof DA Dose replacement therapy per day in three equally divided lots canincrementally reduce their total dose of DA replacement therapy by ¼ to½ dose increments while balancing therapeutic effects and adverseeffects. D6. Time of Exposure to light should commence between the hoursPhototherapy of 7:00 p.m. and 10:00 p.m. Drug regimens should not bealtered until an observation period of 2-4 weeks has been undertaken andthe patient is in compliance. D7. Duration The duration of phototherapyshould last for 1 hour and of should be undertaken daily. PhototherapyD8. Frequency The frequency of emission should be polychromatic andIntensity light with an intensity of about 1,000 lux to about 1,500 ofEmission lux.

TABLE 7 sets forth a protocol that may be followed under circumstanceswhere a patient experiences secondary symptoms and side effects of DAreplacement therapy, such as depression, insomnia or anxiety. Theprotocol set forth by TABLE 10 may also be followed to reduce theconsequences of polypharmacy in a patient.

TABLE 7 Example Conditions for Photo-Pharmacological Intervention in APatient ExperiencingSecondary Symptoms Such As Insomnia, Depression andAnxiety Rule to Reduce Polypharmacy PAD1. In patients that have beenmaintained on DA replacement Treatment therapy, are experiencingsecondary symptoms such as Response depression, insomnia or anxiety andare undergoing drug Stabilization treatment for such conditions, it isimportant that their (TRS) conditions and treatments be clearlyidentified and stable before commencing this program. PAD2 After theadministration of phototherapy for at least four Withdrawing weeks, itseffects on depression, anxiety and insomnia Anxiolytic, should becarefully assessed. If these conditions have Antidepressant stabilizedor improved, the daily dosage of drugs and Soporific administered forthese conditions can be gradually Medications reduced by ¼ to ½increments as the antidepressant, anxiolytic or soporific effects ofphototherapy take effect. Careful monitoring of affect, sleep andanxiety must be undertaken professionally PAD3. Time of In the firstinstance, exposure to light should commence Phototherapy between thehours of 7:00 p.m. and 10:00 p.m. Drug regimens should not be altereduntil an observation period of 2-4 weeks has been undertaken and thepatient is in compliance. PAD4. The duration of phototherapy should lastfor 1 hour and Duration of should be undertaken daily. PhototherapyPAD5. The frequency of emission should be polychromatic light Frequencyand with an intensity of about 1,000 lux to about 1,500 lux. Intensityof Emission

When a patient experiences tolerance to drug therapies, a protocol suchas that set forth in TABLE 8 may be followed.

TABLE 8 Example Conditions for Photo-Pharmacological Intervention in APatient Experiencing Tolerance to DA Replacement Therapy, Includingwearing off, Freezing Rule and Between-Dose Loss of Efficacy T1.Treatment In patients that have been maintained on DA replacementResponse therapy and are experiencing secondary symptoms such asStabilization depression, insomnia or anxiety and are undergoing (TRS)treatment with drugs for such conditions, it is important that theirconditions and treatments be clearly identified and stable beforecommencing this program. T2 After the application of phototherapy for atleast four Withdrawing weeks, the effects of phototherapy on depression,anxiety Anxiolytic, and/or insomnia should be carefully assessed. Ifthese Antidepressant conditions have stabilized or improved, as the andSoporific antidepressant, anxiolytic or soporific effects of Medicationsphototherapy take effect, the daily doses of the administered drug canbe gradually reduced by ¼ to ½ increments. Careful monitoring of affect,sleep and anxiety must be undertaken professionally. T3. Time of In thefirst instance, exposure to light should commence Phototherapy betweenthe hours of 7:00 p.m. and 10:00 p.m. Drug regimens should not bealtered until an observation period of 2-4 weeks has been undertaken andthe patient is in compliance. T4. Duration of The duration ofphototherapy should last for 1 hour and Phototherapy should beundertaken daily. T6. Frequency The frequency of emission should bepolychromatic light and Intensity of with an intensity of about 1,000lux to about 1,500 lux. Emission

TABLE 9 provides an example of a process for assessing and treating PDover long periods of several months to years with the purpose of slowingor preventing the ongoing degenerative process so as to keep thesymptoms of a PD patient from worsening.

TABLE 9 Conditions for Long-Term Photo-Pharmacological Rule Interventionto Prevent Progression of the Disease Process LT1. Patients should bemonitored as described above in response Treatment to their daily drugregimen for primary motor symptoms Response and should remain stablewith as few changes to their drug Stabilization regimen as possible forthe duration of treatment. LT2 Light exposure should occur daily at thetime required to Conditions of achieve optimal therapeutic response. Thenumber of Treatment omissions should not exceed one every two weeks, andchanges to DA replacement therapy should be avoided. If the patient mustbe brought back into control by use of drugs, then the dose required todo so should be titrated by ¼ to ½ doses and applied at strategic times,as defined in TABLE 7. LT3. Time of Exposure to light should commencebetween the hours of Phototherapy 7:00 P.M. and 10:00 pm. Drug regimensshould not be altered until an observation period of 2-4 weeks has beenundertaken and the patient in compliant with phototherapy and titration.

FIGS. 1 through 4 depict the effects of combining melatonin regulationtherapies, such as light therapy, with drug therapy to treatmotor-related neurological conditions.

In a specific embodiment, when drug and light therapies are combined,100 mg of L-dopa may be administered to a subject three (3) times daily,with administration of the first dose occurring approximately thirty(30) minutes prior to symptom onset, and the last dose beingadministered at about 5:30 p.m. When the subject suffers from PD, thesubject will typically remain asymptomatic for about the same amount oftime every morning after he or she wakes (e.g., about an hour, up tothree (3) hours, etc.). Thus, the subject will know when symptoms willstart to occur during the day and, therefore, will know when to take thefirst dose of L-dopa.

Depending upon the severity of symptoms experienced by a particularsubject, higher dosages of L-dopa may be required. FIG. 21 depicts thestandard dosages of L-dopa (and a variety of other dopamine derivatives)that are prescribed for subjects who suffer from varying degrees ofParkinson's disease. Nevertheless, when drug and light therapy are usedtogether in accordance with teachings of the present invention,below-standard L-dopa dosages may be administered to a subject.

Of course, the same rationale may be applied to other dopaminederivative therapies by substituting an equivalent dosage of the otherdopamine derivative for 100 mg of L-dopa (see, e.g., FIG. 21, whichdepicts equivalent dosages for a variety of dopamine derivatives).Similar drug dosages may also be applied to other motor-relatedneurological conditions.

In the graph of FIG. 1, the effects of light therapy alone and with drugtreatment on a newly diagnosed, or de novo, Parkinson's disease patientare illustrated. On the left side of the graph, the tremors experiencedby the patient were evaluated. Specifically, a visual analog scale wasused to quantify the patient's tremors. The tremors initiallyexperienced by the patient (labeled “March 18”) are compared with thetremors experienced by the patient after eight (8) weeks of lighttherapy alone (daily ocular exposure to bright white light at anintensity of about 1,000 lux to about 1,500 lux) (labeled “May 12”) andthe tremors experienced by the patient after another eight (8) weeks oflight therapy in conjunction with drug therapy (labeled “June 9”). Withlight therapy alone, the patient's tremors decreased by about 20%. Whenlight therapy was used in conjunction with drug therapy, the subject'stremors decreased by 56%.

On the right side of the graph of FIG. 1, micrographia, or a progressivedecrease in the patient's handwriting, which is symptomatic ofmotor-related neurological conditions, such as PD, was evaluated. Thediagonal distance across a routine sample of signature was measured.During the initial test, the diagonal measure of the patient'shandwriting measured 16 mm. After eight (8) weeks of light therapy, thesize of the patient's handwriting measured 19 mm. Eight (8) weeks afterthe addition of drug therapy, the diagonal measure of the patient'shandwriting exhibited a further increase—to 25 mm.

The decreases in tremors and micrographia (i.e., the increase inhandwriting size) demonstrate the therapeutic value of using lighttherapy alone or in combination with pharmacological treatment. Thefollowing results specifically illustrates that a long-term regimen oflight therapy and drug treatment in accordance with teachings of thepresent invention can have a disease-modifying effect on (e.g., slow orhalt the progression of, etc.) a degenerative neurological disease.

FIG. 2a shows the effects of light therapy on a patient who had beenreceiving dopamine replacement therapy (i.e., drugs) for several years.The indicators of the effectiveness of light therapy included a “latencyto walk” exercise, in which the time it took the patient to walk adistance of three meters then return was measured; a “fist to elbowlatency” analysis was conducted, in which the time it took the patientto repeatedly move his or her hand from the first to the elbow of thepatient's other, vertically oriented arm (FIG. 5) ten times wasmeasured; and a “floor to knee latency” analysis was conducted, in whichthe time it took the patent to raise his or her foot from the floor toknee level (FIG. 6) ten times was measured. The results of the latencyto walk tests are depicted as squares (▪) in the graph of FIG. 2a . Theresults of the fist to elbow latency tests appear as triangles (▴) inthe graph of FIG. 2a . The results of the floor to knee latency analysesare depicted as circles () in the graph of FIG. 2 a.

All three tests were conducted at three distinct times: (1) apre-assessment before the initiation of light therapy; (2) a secondsession after the patient received daily light therapy for about seven(7) weeks; (3) a third session after the patient received daily lighttherapy for an additional eleven (11) weeks; and (4) a fourth sessionabout twenty (20) weeks later, during which light therapy treatmentswere occasionally skipped. All three of the measures that had beenevaluated exhibited improvement over the course of treatment, includingstriking initial rates of improvement and overall improvements of 21%,25%, and 33% for the latency to walk, fist to elbow latency, and floorto knee latency, respectively, measured in decreases in the time it tookthe patient to perform the prescribed exercises.

FIG. 2b demonstrates the improvements achieved in a patient's ability tocomplete the floor to knee latency exercise over the course of a regimenof light therapy administered in conjunction with previously prescribedDA replacement therapy. Again, a measured improvement of about 30%,measured in terms of a decrease in the time it took the patient tocomplete the exercise, was observed.

The chart of FIG. 3 shows the results of light therapy on a subject whohad been receiving DA replacement therapy for a prolonged period oftime, but continued to experience severe involuntary movements(dyskinesia). After about six months of light therapy, in addition tocontinued DA replacement therapy, the patient's dyskinesia diminished byabout 80%.

In the graph of FIG. 4, the effects of light therapy, in conjunctionwith continued drug (DA replacement) therapy, on various secondarysymptoms of motor-related neurological conditions or side effects of DAreplacement therapy. Specifically, the effects of light therapy (withcontinued drug therapy) on insomnia (♦), nocturnal movement (▴),depression (▪), and anxiety () are shown. Specifically, the graph ofFIG. 4 shows that the addition of light therapy to a regimen ofpharmacological treatment decreased anxiety by 58%, insomnia by 66%,nocturnal movement by 95%, and depression by 100%.

In addition to the individualized results depicted by FIGS. 1-4, alarger-scale study was conducted. In that study, polychromatic lighttherapy was administered to subjects who were receiving drug treatmentfor motor-related neurological conditions. Specifically, light therapy,in the form of polychromatic light having peaks at about 435 nm to about436 nm, about 460 nm to about 520 nm, about 540 nm to about 560 nm, andabout 640 nm was administered at an intensity of about 1,000 lux toabout 1,500 lux. The irradiance of the blue-green light present in thelight administered to each subject was about 280 μW/cm², while theirradiance of the red light present in that light was only about 150μW/cm².

The study, which had a duration of forty-three (43) months, involved 94subjects. The subjects were divided into two groups: (A) thirty-one (31)Parkinson's disease patients who received standard drug therapy, but notlight therapy; and (B) sixty-three (63) Parkinson's disease patients whoreceived light therapy in addition to drug therapy, in the manner setforth in TABLE 8.

A variety of factors, including primary symptoms of Parkinson's diseaseand other motor-related neurological conditions (e.g., balance (FIG. 7),bradykinesia (FIG. 8), fist to elbow latency (FIG. 9), latency to walk(FIG. 10) and tremor (FIG. 11), rigidity (FIG. 12), nocturnal movementand dyskinesia (FIG. 13), etc.) and secondary symptoms of Parkinson'sdisease and other motor-related neurological conditions (e.g., anxiety(FIG. 14), insomnia (FIG. 15), etc.) were evaluated at the outset of thestudy, and at periodic intervals throughout the study. As illustrated byFIGS. 7-15, when only drug treatment was provided, all of these symptomsbut latency to walk (FIG. 10) either remained the same or worsened overtime. When light therapy was added to drug therapy, a significantdecrease in the severity of all of the symptoms was realized (latency towalk—FIG. 10—improved at about the same rate in both groups ofsubjects).

In another study, the effects of yellow-green light on subjects whosuffered from Parkinson's disease were evaluated. In that study, whichwas conducted on seven (7) subjects over an eight (8) month period oftime, light therapy was administered by positioning a yellow-greenfilter over the light source (e.g., a filter available from LEE Filtersof Hampshire, UK; a filter available from GAM Products, Inc. of LosAngeles, Calif.; a filter available from Cotech Sensitising Ltd. ofTedegra, Gwent, South Wales, UK; etc.). When a yellow-green filter isused in conjunction with a polychromatic light source such as theBRITELITE 6 energy light available from Koninklifke Philips ElectronicsN.V., it will filter out at least some visible light having wavelengthsof more than 570 nm and at least some visible light having wavelengthsthat are less than 520 nm, as shown in the spectral power distributiongraphs of FIG. 16 (unfiltered light) and FIG. 17 (filtered light). Morespecifically, FIGS. 16 and 17 show that the filter allows a peak thatextends from 537 nm to 560 nm to pass, while attenuating significantamounts of light generated by the light source below 520 nm and in therange of 575 nm to 640 nm. The narrow band isolated intensity of thegreen light (i.e.., light having one or more wavelengths of 520 nm to570 nm) at each subject's eyes was about 880 lux, and included anabove-ambient amount (an irradiance of about 130 μW/cm²) of visiblelight having wavelengths of about 520 nm to 570 nm and a below-ambientamount (an irradiance of about 40 μW/cm²) of visible light havingwavelengths of more than 570 nm. As shown in FIGS. 18 and 19, theadministration of light therapy in this manner resulted in gradual,consistent improvements in the primary symptoms of Parkinson's diseaseand many other motor-related neurological conditions, as evaluated byfist to elbow latency, knee to floor latency and latency to walk tests(FIG. 18), and evaluation of each subject's arm swing, the severity ofeach subject's tremors and nocturnal movement by each subject (FIG. 19).Secondary symptoms of motor-related neurological conditions were alsoimproved, as represented by the evaluation of anxiety shown in FIG. 19.

Turning now to FIG. 20, long-term light therapy has an effect on thedrug dosages that are needed to address the symptoms of subjects whosuffer from motor-related neurological conditions. FIG. 20 is a graphthat depicts the drug dose requirements of various groups of subjects atthe beginning (“Before”) and end (“After”) of the forty-three (43) monthstudy.

The first (left-most) pair of bars on graph represents the drug dosagesrequired by Parkinson's disease patients who did not receive lighttherapy. At the outset of the study, these subjects received, onaverage, 833 mg of L-dopa each day. After forty-three (43) months, theaverage drug dosage per-subject increased to 1142 of L-dopa each day.This represents a drug burden increase of about thirty-seven percent(37%) over forty-three (43) months. As shown in FIGS. 7-15, althoughdrug dosages were increased over time, the symptoms of the motor-relatedneurological conditions suffered by these subjects actually worsenedwith time.

The second pair of bars represents the drug dosages administered tosubjects who also received long-term periodic light therapy for theirmotor-related neurological conditions. On average, drug dosages weresubstantially constant (e.g., an increase of only about two percent(2%), etc.) over the forty-three (43) month study, with the initialaverage daily L-dopa dosage being about 969 mg and the final averagedaily L-dopa dosage being about 990 mg. Over that time, as shown inFIGS. 7-15, most of the symptoms of the motor-related neurologicalconditions suffered by the subjects who received light therapy improved(i.e., decreased in severity) significantly, even without anysubstantial increase in drug dosage.

As illustrated by the third, fourth and fifth pairs of bars in the graphof FIG. 20, the need for higher drug dosages over time decreased as thesubject's compliance with prescribed light therapy regimens increased.As indicated by the fourth pair of bars, subjects who were“semi-compliant” (i.e., subjects who occasionally skipped a lighttherapy session or cut light therapy sessions short) initially requiredan average of 1056 mg of L-dopa each day and, at the end of the study,required an average of 1094 mg of L-dopa each day (a dosage increase ofabout three and a half percent (3½%)). Subjects who were more compliant(i.e., subjects who skipped or cut short a light therapy session lessthan once a week)—shown as the third pair of bars—initially required, onaverage, 910 mg of L-dopa per day and by the end of the study required,on average, 926 mg of L-dopa per day (a dosage increase of less than twopercent (2%)). Subjects who rarely, if ever (i.e., less than once amonth), skipped or cut short a light therapy session required, onaverage, only three (3) more milligrams of L-dopa at the end of thestudy (591 mg/day) than they did at the beginning of the study (588mg/day) (about a half a percent (½%) increase).

The data provided in FIG. 20 indicate that, when light therapy isprovided on a substantially regular basis to a subject who suffers froma motor-related neurological condition, the dosages of drugsadministered to the subject may remain substantially the same overprolonged periods of time (e.g., a year or more, three years, fouryears, five years, etc.). In addition, when considered in conjunctionwith FIGS. 7-15, the data of FIG. 20, suggest that a combination of drugtherapy and light therapy in accordance with teachings of the presentinvention may enable a reduction in drug dosages while preventing anyincreases (and, in some cases, actually decreasing) the severity ofsymptoms experience by a subject who suffers from a motor-relatedneurological condition.

These results demonstrate that the addition of light therapy inaccordance with teachings of the present invention to the overalltreatment regimen for subjects who are long-term sufferers of at leastone motor-related neurological condition may abate symptoms of themotor-related neurological condition. This improvement in a subject'squality of life may be maintained by continuing to provide the subjectwith light therapy and drug therapy, with the added possibility ofreduced drug dosages or reducing the rate at which drug dosages areincreased over time. Combining strategic light therapy with drug therapymay also stop the progression of motor-related neurological conditions.

In addition to methods for addressing motor-related neurologicalconditions, the present invention includes techniques for diagnosingmotor-related neurological conditions. Such a technique may includeexposing a subject to certain wavelengths of light (e.g., amber, orange,red, etc.) without exposing the subject to other wavelengths of light(e.g., blue, blue-green, green, etc.). These wavelengths may temporarilyinhibit dopaminergic activity. For example, melatonin production ormelatonergic activity by a subject may be temporarily increased. Atemporary increase in melatonergic activity may temporarily exacerbatethe symptoms of a motor-related neurological condition, which mayfacilitate a physician's diagnosis of the motor-related neurologicalcondition. This same phenomenon may be elicited, in some embodiments, byadministering increased levels or isolated levels of amber, orangeand/or red light (e.g., about the same or greater levels of amber,orange and/or red light than is present in ambient indoor light, at agreater collective intensity than blue, blue-green and/or green light,with wavelengths from 570 nm to 750 nm having a greater collectiveintensity than the collective intensity of wavelengths from 460 nm to570 nm, etc.) to the subject.

In some embodiments, certain wavelengths of light may be filtered orotherwise removed from the light that is administered to a subject whois predisposed to or who may be suffering from a motor-relatedneurological condition. Without limiting the scope of the presentinvention, wavelengths of 570 nm or less may be removed from thediagnostic light. These wavelengths may include green and/or blue-greenwavelengths of light. In other embodiments, levels of administered lighthaving wavelengths above 570 nm or levels of light having wavelengths ofabove 570 nm to 750 nm may exceed levels of administered light withwavelengths of 570 nm or less. In some embodiments, the subject may beexposed to one or more isolated bandwidths of amber, orange and/or redlight.

In the event that physician determines that the subject is likely tosuffer from a motor-related neurological condition or suffers from amotor-related neurological condition, the physician may prescribe acourse of treatment for the diagnosed condition. A prescribed course oftreatment may include, among other things, stimulating a dopaminergicresponse by the subject's body, which may adjust levels of one or moremonoamines within the subject's body (e.g., one or more of the subject'smelatonin, serotonin and/or dopamine levels, etc.). This may be done inany suitable manner, for example, with ocular light therapy alone or inconnection with the administration of one or more drugs, and/or othersuitable treatments.

One specific embodiment of a process for expediting the diagnosis of amotor-related neurological condition, such as PD, is described in TABLE10.

TABLE 10 Conditions for Early Diagnosis and Developing A Rationale forEarly Treatment Thereby Preventing the Rule Onset and Worsening of PDED1. PD Patients and undiagnosed patients should be Treatment monitoredas described above in response to their daily Response drug regimen forprimary motor symptoms and should Stabilization remain stable with asfew changes to their drug regimen as possible for the duration oftreatment or observation ED2 Exposure to red light should occur daily atthe same time Conditions of each day, usually in the evening. The numberof Treatment omissions should not exceed one day every two weeks.Changes to DA replacement therapies and other medications should beavoided. ED3. Time of Exposure to light should commence between thehours Phototherapy of 7:00 p.m. and 10:00 p.m. Drug regimens should notbe altered until an observation period of 2-4 weeks has been undertakenand the patient is in compliance with phototherapy and titration. Thecondition and well-being of the patient is monitored twice weekly duringthe course of treatment and terminated as soon as symptoms are manifest.

FIG. 21 is a chart that shows the relative effects of polychromaticlight and red light on the following Parkinson's disease symptoms:Agitation, anxiety, features on challenge, bradykinesia, depression,dreaming, dyskinesia, irritability, mood swing, rigidity, sleep andtremor will be exacerbated.

As shown in the left side of the chart, treatment with polychromaticlight (daily treatment for one hour at an intensity of about 1,000 luxto about 1,500 lux) improved an average of sixteen (16) known PDsymptoms in the treated patients, while treatment with red lightyielded, on average, no improvement in PD symptoms in the treatedsubjects. Rather, as illustrated by the right side of the chart of FIG.21, exposure to red light exacerbated about eleven (11) symptoms in thetreated subjects, while polychromatic light only exacerbated an averageof two known PD symptoms in the treated patients.

From these results, the utility of using red light (or amber and/ororange light) to enable early detection of motor-related neurologicalconditions is apparent. In addition, it can be seen that the red portionof polychromatic light may have detrimental effects on patients whosuffer from motor-related neurological conditions.

In a specific embodiment, a subject who is believed to be prone to amotor-related neurological condition or who may be suffering from theearly stages of a motor-related neurological condition may be subjectedto diagnostic therapy. Such diagnostic therapy may be affected byexposing the subject to one or more of red, orange and/or amber light.The light may be administered to the eyes of the subject. In someembodiments, repeated (e.g., daily, three times a week, etc.)administrations for prolonged periods of time (e.g., one week, twoweeks, one month, etc.) may be useful in providing an accuratediagnosis.

FIG. 22 illustrates the effects of light therapy along with drug therapyto treat Parkinson's disease. A long-term coefficient (LT_(coeff)) wascalculated using the following formula:

LT _(coeff).=(n _(SI)(+1)+n _(SD)(−1)+n _(SNC)(0))/n _(SI) +n _(SD) +n_(SNC),

where n_(SI) is the number of symptoms showing improvement, n_(SD) isthe number of symptoms showing deterioration, and n_(SNC) is the numberof symptoms showing no change. The long-term coefficient may enable asubject to better recognize his or her progression as treatment inaccordance with teachings of the present invention continues over time,particularly for symptoms where improvements are very gradual, andpossibly imperceptible on a day-to-day basis. In some embodiments, thelong-term coefficient or any other means for quantifying a subject'sprogress may be embodied by a computerized feedback system.

Although the foregoing description contains many specifics, these shouldnot be construed as limiting the scope of the invention or of any of theappended claims, but merely as providing information pertinent to somespecific embodiments that may fall within the scopes of the inventionand the appended claims. Features from different embodiments may beemployed in combination. In addition, other embodiments of the inventionmay also be devised which lie within the scopes of the invention and theappended claims. The scope of the invention is, therefore, indicated andlimited only by the appended claims and their legal equivalents. Alladditions, deletions and modifications to the invention, as disclosedherein, that fall within the meaning and scopes of the claims are to beembraced by the claims.

What is claimed:
 1. A method for addressing a motor-related neurologicalcondition, comprising: diagnosing a motor-related neurological conditionexperienced by a subject; and prescribing a light therapy.
 2. The methodof claim 1, wherein prescribing the light therapy comprises prescribingan enriched course of light therapy for the subject including anabove-ambient peak in at least one of a blue range of wavelengths, agreen range of wavelengths, and a blue-green range of wavelengths and abelow ambient amount of amber, orange or red wavelengths.
 3. The methodof claim 2, wherein prescribing comprises prescribing the enrichedcourse of light therapy with the above-ambient peak having anabove-ambient narrow band isolated intensity.
 4. The method of claim 2,wherein prescribing the light therapy comprises prescribing an amber,orange or red light deficient course of light therapy for the subject.5. The method of claim 1, wherein prescribing comprises prescribing agreen light enriched course of light therapy having an above-ambientamount of green light.
 6. The method of claim 1, wherein prescribing thelight therapy comprises prescribing an enriched course of light therapyfor the subject including at least one above-ambient peak in a range of460 nm to 570 nm.
 7. The method of claim 6, wherein prescribing thelight therapy comprises prescribing the enriched course of light therapyfor the subject with the at least one above-ambient peak being in arange of 520 nm to 570 nm.
 8. The method of claim 6, wherein prescribingthe light therapy comprises prescribing the enriched course of lighttherapy with a below-ambient amount of light in a range of above 570 nmto 750 nm.
 9. The method of claim 1, wherein prescribing the lighttherapy includes prescribing at least one time of day and at least oneduration light therapy is to be administered to the subject.
 10. Themethod of claim 9, wherein prescribing the light therapy comprisesprescribing a same spectral makeup of the light therapy for a pluralityof times throughout each day.
 11. The method of claim 9, whereinprescribing the light therapy comprises prescribing a plurality of timedependent spectral makeups of the light therapy, with one time dependentspectral makeup of the plurality of time dependent spectral makeupscorresponding to at least one particular time during the day.
 12. Themethod of claim 1, wherein prescribing light therapy includesprescribing light therapy for stimulating a dopaminergic response. 13.The method of claim 1, wherein diagnosing comprises ocularly exposingthe subject to at least one diagnostic bandwidth of light.
 14. Themethod of claim 13, wherein ocularly exposing enhances at least onesymptom of at least one motor-related neurological condition.
 15. Themethod of claim 13, wherein ocularly exposing comprises administering atleast one wavelength of light within a range of greater than 570 nm toabout 750 nm to the subject.
 16. The method of claim 15, whereindiagnosing includes ocularly exposing the subject to light in whichwavelengths of greater than 570 nm to 750 nm have a greater collectiveintensity than a collective intensity of wavelengths from 460 nm to 570nm.
 17. The method of claim 16, wherein ocularly exposing enhances atleast one symptom of at least one motor-related neurological condition.18. The method of claim 13, wherein diagnosing includes ocularlyexposing the subject to an isolated bandwidth of at least one of amber,orange and red light.
 19. The method of claim 1, further comprising:prescribing a drug therapy including a dosage of medication for treatingthe motor-related neurological condition.
 20. The method of claim 19,further comprising: after repeatedly administering the light therapy,reducing a dose of the medication administered to the subject in arevised course of treatment to treat the motor-related neurologicalcondition.
 21. The method of claim 19, wherein prescribing the lighttherapy and prescribing the drug therapy comprise prescribing the lightand drug therapies in accordance with an optimal dosing schedule. 22.The method of claim 21, wherein prescribing the light and drug therapiesin accordance with the optimal dosing schedule comprises prescribing thelight and drug therapies in such a way that the light therapy isadministered at a different time of the day than the drug therapy. 23.The method of claim 21, wherein prescribing the light and drug therapiesin accordance with the optimal dosing schedule comprises terminatingadministration of the drug therapy at predetermined time of day.
 24. Amethod for addressing a motor-related neurological condition,comprising: receiving a prescription for light therapy for addressing amotor-related neurological condition experienced by a subject; andadministering the light therapy.
 25. The method of claim 24, whereinadministering comprises administering the light therapy once each day.26. The method of claim 24, wherein administering comprisesadministering light including an above-ambient intensity of at least onebandwidth having a peak in a range of 520 nm to 570 nm.
 27. The methodof claim 26, wherein administering comprises administering light lackingan above-ambient intensity of any wavelength in a range of greater than570 nm to 750 nm.
 28. The method of claim 26, wherein administeringcomprises administering light lacking an above-ambient intensity of anywavelength in a range of 440 nm to 490 nm.
 29. The method of claim 24,wherein administering comprises ocularly administering the course oflight therapy to the subject.
 30. The method of claim 24, furthercomprising: receiving a prescription for drug therapy including a dosageof medication for addressing the motor-related neurological condition;and administering the drug therapy.
 31. The method of claim 30, whereinadministering the drug therapy comprises administering the dosage ofmedication a plurality of times each day.
 32. A system for addressing amotor-related neurological condition, comprising: a medication fortreating a motor-related neurological condition or at least one symptomof the motor-related neurological condition; and a light therapy devicefor ocularly delivering light with at least one peak at a wavelengththerapeutic for the motor-related neurological condition or the symptomof the motor-related neurological condition.
 33. The system of claim 32,wherein the light therapy device delivers the light while deliveringbelow-ambient levels of light that exacerbate the motor-relatedneurological condition or the symptom of the motor-related neurologicalcondition.
 34. A method for diagnosing a motor-related neurologicalcondition, comprising: ocularly exposing a subject to at least one ofamber, orange and red light in a manner that will cause the subject toexhibit at least one symptom of a motor-related neurological conditionif the subject is predisposed to suffer from the motor-relatedneurological condition.
 35. The method of claim 34, wherein ocularlyexposing temporarily exacerbates at least one symptom of the at leastone motor-related neurological condition.
 36. The method of claim 34,wherein ocularly exposing enables a physician to distinguish betweendifferent motor-related conditions or to determine a severity of amotor-related condition.
 37. The method of claim 34, wherein ocularlyexposing comprises administering to the subject light comprising one ormore isolated bandwidths with peaks centered at at least one of amber,orange and red light.
 38. The method of claim 37, wherein administeringcomprises administering one or more isolated bandwidths within a rangeof greater than 570 nm to about 750 nm to the subject.
 39. The method ofclaim 38, wherein administering comprises filtering light of wavelengthsof 570 nm and below from light administered to the subject.
 40. A methodfor addressing a motor-related neurological condition, comprising:ocularly administering blue light and/or green light to a subject. 41.The method of claim 40, wherein ocularly administering blue light and/orgreen light to the subject comprises ocularly administering anabove-ambient amount of blue light and/or an above-ambient amount ofgreen light to the subject.
 42. The method of claim 41, whereinbelow-ambient amounts of yellow, orange, and red light are administeredto the subject.
 43. A method for addressing a motor-related neurologicalcondition, comprising: ocularly administering at least one bandwidth oflight having a peak in a range of 460 nm to 570 nm to a subject.
 44. Themethod of claim 43, wherein ocularly administering comprises ocularlyadministering at least one bandwidth of light having a peak in a rangeof 520 nm to 570 nm to the subject.
 45. The method of claim 43, whereinocularly administering comprises ocularly administering an above-ambientamount of the light having the peak in range of 460 nm to 570 nm. 46.The method of claim 45, wherein below-ambient amounts of light havingwavelengths in a range of greater than 570 nm to 750 nm are administeredto the subject.